The behavioral pharmacological profile of a drug in a pertinent species is necessary for evaluating quantitatively how the drug functions as a reinforcer and how use or abuse of the drug effects other aspects of the subject's behavior. Ongoing studies on the direct behavioral effects of drugs include a number of different paradigms. A variety of studies involve observations of changes in spontaneous and learned behavior following acute or chronic injections of drugs. For example, we have recently shown that the cocaine metabolizing enzyme butyrylcholinesterase (BChE) systemically administered to rats can attenuate the locomotor activating (psychomotor stimulant) effect of cocaine. This result is most probably due to the enzyme's ability to shorten the duration of action for cocaine. Added to rat plasma, BChE dramatically shortened cocaine's half-life. Further, the enzyme altered the metabolic pattern such that the relatively non-toxic metabolite ecgonine methyl ester was produced, rather than benzoylecgonine. BChE itself had no effect on locomotor activity. These results suggest that BChE should be evaluated as a treatment for cocaine abuse and addiction. A wide range of other studies are ongoing to investigate pharmacological mechanisms that determine how psychoactive drugs such as nicotine, methamphetamine, and cocaine function as discriminative stimuli or effect ongoing learned behavior. In one series of studies we are using laboratory animals to characterize nicotine-caffeine interactions under conditions of chronic caffeine exposure. Using a variety of behavioral techniques such as self-administration, drug discrimination and fixed-intervals schedule of food reinforcement that are commonly used to investigate the behavioral effects of psychostimulants we have demonstrated that chronic caffeine exposure in the drinking water of rats appears to (1) markedly enhance acquisition of IV nicotine self-administration, (2) qualitatively change the discriminative cue of nicotine without altering the rate of acquisition of a nicotine discrimination, but (3) has little impact on the effects of nicotine on schedule-controlled food maintained responding. In general, the results obtained in our laboratory thus far, clearly reveal a rather complex pattern of nicotine-caffeine interactions which appears to depend upon the particular aspect of behavior under examination. The results obtained in these laboratory experiments may aid in better understanding of nicotine-caffeine interactions in humans.